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Title: S-nitrosocaptopril nanoparticles as nitric oxide-liberating and transnitrosylating anti-infective technology.

Authors: Mordorski, Breanne; Pelgrift, Robert; Adler, Brandon; Krausz, Aimee; da Costa Neto, Alexandre Batista; Liang, Hongying; Gunther, Leslie; Clendaniel, Alicea; Harper, Stacey; Friedman, Joel M; Nosanchuk, Joshua D; Nacharaju, Parimala; Friedman, Adam J

Published In Nanomedicine, (2015 Feb)

Abstract: Nitric oxide (NO), an essential agent of the innate immune system, exhibits multi-mechanistic antimicrobial activity. Previously, NO-releasing nanoparticles (NO-np) demonstrated increased antimicrobial activity when combined with glutathione (GSH) due to formation of S-nitrosoglutathione (GSNO), a transnitrosylating agent. To capitalize on this finding, we incorporated the thiol-containing ACE-inhibitor, captopril, with NO-np to form SNO-CAP-np, nanoparticles that both release NO and form S-nitrosocaptopril. In the presence of GSH, SNO-CAP-np demonstrated increased transnitrosylation activity compared to NO-np, as exhibited by increased GSNO formation. Escherichia coli and methicillin-resistant Staphylococcus aureus were highly susceptible to SNO-CAP-np in a dose-dependent fashion, with E. coli being most susceptible, and SNO-CAP-np were nontoxic in zebrafish embryos at translatable concentrations. Given SNO-CAP-np's increased transnitrosylation activity and increased E. coli susceptibility compared to NO-np, transnitrosylation rather than free NO is likely responsible for overcoming E. coli's resistance mechanisms and ultimately killing the pathogen. FROM THE CLINICAL EDITOR: This team of authors incorporated the thiol-containing ACE-inhibitor, captopril, into a nitric oxide releasing nanoparticle system, generating nanoparticles that both release NO and form S-nitrosocaptopril, with pronounced toxic effects on MRSA and E. coli in the presented model system.

PubMed ID: 25461287 Exiting the NIEHS site

MeSH Terms: Anti-Infective Agents/administration & dosage; Anti-Infective Agents/chemistry; Captopril/administration & dosage; Captopril/analogs & derivatives; Captopril/chemistry; Escherichia coli/drug effects; Escherichia coli/pathogenicity; Glutathione/metabolism; Humans; Immune System/drug effects*; Methicillin-Resistant Staphylococcus aureus/drug effects*; Methicillin-Resistant Staphylococcus aureus/pathogenicity; Nanoparticles/administration & dosage*; Nanoparticles/chemistry; Nitric Oxide/administration & dosage*; Nitric Oxide/chemistry; Staphylococcal Infections/drug therapy; Staphylococcal Infections/microbiology

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